The dopamine transporter (DAT) has been previously identified as a principal brain receptor site that has been correlated with the rewarding and euphoric properties of cocaine. It is required for the actions of each of the current dopamine-selective toxins that produce the best models of Parkinson's disease. Analyses of DAT structure-function relationships continued during this FY with further characterization of the roles of nonpolar aromatic amino acids, especially phenylalanines and prolines, in transporter function. These studies continue to identify selective DAT regions important for cocaine analog recognition or for dopamine transport. These insights help in design and identification of selective structure-function features of small molecule compounds possibly active in vivo as cocaine antagonists. These analyses revealed candidate compounds with significant selectivity for cocaine analog recognition compared with dopamine uptake and reduced cross-reactivity with other sites. One of these compounds can serve as an apparent partial cocaine antagonist in vivo, blocking cocaine-induced locomotion in mice. It is less reliable in reducing cocaine-conditioned place preferences or reducing the breakpoint of a non-human primate response for cocaine self-administration.